298 Domiciliary periodic Levosimendan infusions in advanced heart failure: a single centre experience

Aims There are several studies that describes a possible use of periodical infusions of Levosimendan in patients with advance heart failure (AHF). In these studies, Levosimendan was administered in ambulatory settings (LevoRep, LION-HEART) or during 24 h of hospital stay (LAICA) and for a maximum of 12 months. Currently there is no strong evidence about the feasibility and safety of performing the infusions in an out of hospital setting. Aim of our study was to analyse the feasibility and safety of periodical Levosimendan infusions in AHF patients, in an out of hospital setting for palliative use. Methods and results Aretrospective study was conducted from June 2016 to September 2021 on AHF patients, followed by our centre for periodic infusion of Levosimendan. All patients were previously implanted with an ICD, were ineligible for heart transplant or for ventricular assist devices. All patients on each cycle underwent a cardiological evaluation, a blood sample (complete blood count, biochemical profile, coagulation profile, and NTproBNP), and Levosimendan was administrated with a wearable infusion pump (CADD-Legacy®; Smiths Medical). The patient went home and came back the day after, to return the pump and for reassessment. We collected data on the different infusion regimen, adapted for every patient, and on adverse events during infusions. We enrolled 11 patients with AHF, 9 (82%) of which of ischaemic origin, 2 (18%) were female, median age 72 years (IQR: 64–75), 10 with NYHA class III, 1 with a NYHA class IV, for a total of 231 infusions, with a median Follow-up of 459 days (IQR 132; 783). A total dose of 6.25 mg was administered at 0.05 μg/kg/min in 24 h. In five patients the infusion was of 12.5 mg at 0.1 μg/kg/min rate in 24 h and in other three patients at 0.05 μg/kg/min in 48 h. The median interval between administrations was 21 days (IQR: 14–24.5). Mild adverse events (i.e. that did not contraindicate successive cycles) were 7 on 231 infusions (3.0%): symptomatic hypotension (four cases, 1.7%), loss of consciousness (two cases 0.9%), bleeding for vein access misplacement (one case, 0.4%). No serious adverse event such as sustained or malignant arrhythmia, allergic reaction, or need for hospital admission were recorded. Conclusions The administration of Levosimendan at home with a wearable iv pump is safe and well tolerated. This practice allows to reduce infusion costs of day hospital regime and to lengthen the time available for drug infusion, thus reducing the events caused by a too rapid infusion.

When Minutes Matter: Rapid Infusion in Emergency Care

Purpose of Review This review provides historical context and an update on recent advancements in volume resuscitation for circulatory shock. Emergency department providers who manage critically ill patients with undifferentiated shock will benefit from the insights of early pioneers and an overview of newer techniques which can be used to optimize resuscitation in the first minutes of care. Recent Findings Rapid infusion of fluids and blood products can be a life-saving intervention in the management of circulatory and hemorrhagic shock. Recent controversy over the role of fluid resuscitation in sepsis and trauma management has obscured the importance of early and rapid infusion of sufficient volume to restore circulation and improve organ perfusion. Evidence from high-quality studies demonstrates that rapid and early resuscitation improves patient outcomes. Summary Current practice standards, guidelines, and available literature support the rapid reversal of shock as a key priority in the treatment of hypotension from traumatic and non-traumatic conditions. An improved understanding of the physiologic rationale of rapid infusion and the timing, volume, and methods of fluid delivery will help clinicians improve care for critically ill patients presenting with shock. Clinical Case A 23-year-old male presents to the emergency department (ED) after striking a tree while riding an all-terrain vehicle. On arrival at the scene, first responders found an unconscious patient with an open skull fracture and a Glasgow coma scale score of 3. Bag-valve-mask (BVM) ventilation was initiated, and a semi-rigid cervical collar was placed prior to transport to your ED for stabilization while awaiting air transport to the nearest trauma center. You are the attending emergency medicine physician at a community ED staffed by two attending physicians, two physicians assistants, and six nurses covering 22 beds. On ED arrival, the patient has no spontaneous respiratory effort, and vital signs are as follows: pulse of 140 bpm, blood pressure of 65/30 mmHg, and oxygen saturation 85% while receiving BVM ventilation with 100% oxygen. He is bleeding profusely through a gauze dressing applied to the exposed dura. The prehospital team was unable to establish intravenous access. What are the management priorities for this patient in shock, and how should his hypotension best be addressed?

Real-World Observations and Practical Considerations of Subcutaneous Daratumumab Administration in Multiple Myeloma

Background: Subcutaneous daratumumab (dara-SC) has several advantages over intravenous daratumumab (dara-IV). It has significantly shorter administration time, lower rates of systemic reactions, and smaller administration volume, while maintaining comparable efficacy and safety. Its fixed dosing allows for easier preparation. At our institution, standard approach is to monitor for 4h following the initial dara-SC dose for those at high risk for systemic reactions, defined as no prior dara use, treatment break ≥90d, or any prior history of reactions. We also administer montelukast and fexofenadine for the first 2 doses of dara-SC in addition to the usual standard pre-medications. Herein, we share our experience with dara-SC use in both dara-naïve and dara-exposed patients in order to gain practical insight, such as optimal monitoring duration, considerations for transitioning between dara-IV and dara-SC, and the place of therapy for dara-IV based on adverse events (AEs). Methods: Between June 2020 and June 2021, patients who received at least one dose of dara-SC were identified and their record was reviewed for any systemic reactions, hypersensitivity medication use, and patient reported AEs. Results: Since June 2020, our dara-SC drug use increased from 38% to 91% of all doses. There were 208 patients who received at least 1 dose of dara-SC. Of 208 patients, 99 (47.6%) were dara-naïve and 109 (52.4%) had prior dara exposure - either transitioning from dara-IV on schedule or had dara-IV as a past line of therapy. We identified 124 patients who met the criteria for 4h post dara-SC injection monitoring: dara-naïve (79.8%), treatment break ≥90d (18.5%), or prior history of reactions (1.6%). Only 5 experienced systemic reactions, representing 4% among those at high risk. All reactions were mild requiring minimal intervention and occurred following the first dara-SC dose. Onset of reactions and type of intervention during the 4h monitoring window were: hypotension (2h; fluid), nausea/vomiting (2.5h; hypersensitivity medications), and sinus tachycardia (4h), while 2 patients had transient chest pressure/tightness at home (1 within 24h, 1 between 1-6d following the dose). Eleven patients (5%) receiving dara-SC converted back to dara-IV, with AEs being the most common reason. Diarrhea, fatigue, and injection site reactions were among the most frequent patient-reported AEs. When transitioning back to dara-IV, a 90min rapid infusion rate was used if >4 prior dara doses were given. No infusion-related reactions were observed. Conclusion: The introduction of dara-SC has significantly improved patient experience. We observed a lower rate of systemic reactions compared to previous reports of 10% with first dose of dara-SC. This may be partly due to our strengthened pre-medication strategy. Opportunities exist to further improve and apply practical considerations when administering dara-SC. Based on our results, shortening on-site monitoring time may be feasible. Disclosures O'Donnell: Onocopeptide: Consultancy; Karyopharm: Consultancy; Janssen: Consultancy; Bristol Myer Squibb: Consultancy; Adaptive: Consultancy; Takeda: Consultancy. Branagan: Adaptive: Consultancy; Sanofi-Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Consultancy. Raje: Celgene, Amgen, Bluebird Bio, Janssen, Caribou, and BMS: Other. Yee: GSK: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Bristol Myers Squibb: Consultancy; Adaptive: Consultancy; Oncopeptides: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; Karyopharm: Consultancy.

Safety and Tolerability of a 90-minute Infusion of Originator and Biosimilar Rituximab in Rituximab- Naïve Patients

This study aimed to investigate the safety and tolerability of 90-min rapid infusion of rituximab, originator or biosimilar (Truxima), for rituximab-naïve patients with hematologic malignancy. We undertook a retrospective review of records of 118 patients (81 originator rituximab and 37 Truxima) with hematologic malignancy who had received rituximab rapid infusion from the first cycle of chemotherapy with corticosteroid premedication administration. Most patients had high Ann Arbor stage (80.9%), high International Prognostic Index risk (69.1%), favorable performance status (98.3%), and high lactate dehydrogenase level (78.8%). The patients received a collective total of 717 rapid rituximab infusions, with an average of 6 infusions per patient (range, 1-8). The incidence of infusion-related reactions (IRRs) of any grade and grade 3/4 during first infusion was 21.2% and 0.8%, respectively. No episode of grade 3/4 IRR was observed during the second and subsequent rituximab infusions. Severity and type of IRRs in Truxima administration were comparable to those of originator rituximab. This study suggests that 90-minute rituximab infusion with the first dose of chemotherapy was well tolerated. In terms of IRR, safety profiles of Truxima were comparable to that of originator rituximab, suggesting that Truxima might replace originator rituximab in a rapid infusion setting.

Dantrolene Prevents the Lymphostasis Caused by Doxorubicin in the Rat Mesenteric Circulation

Background and Purpose: Doxorubicin (DOX) is a risk factor for arm lymphedema in breast cancer patients. We reported that DOX opens ryanodine receptors (RYRs) to enact “calcium leak,” which disrupts the rhythmic contractions of lymph vessels (LVs) to attenuate lymph flow. Here, we evaluated whether dantrolene, a clinically available RYR1 subtype antagonist, prevents the detrimental effects of DOX on lymphatic function.Experimental Approach: Isolated rat mesenteric LVs were cannulated, pressurized (4–5 mm Hg) and equilibrated in physiological salt solution and Fura-2AM. Video microscopy recorded changes in diameter and Fura-2AM fluorescence tracked cytosolic free calcium ([Ca2+i]). High-speed in vivo microscopy assessed mesenteric lymph flow in anesthetized rats. Flow cytometry evaluated RYR1 expression in freshly isolated mesenteric lymphatic muscle cells (LMCs).Key Results: DOX (10 μmol/L) increased resting [Ca2+i] by 17.5 ± 3.7% in isolated LVs (n = 11). The rise in [Ca2+i] was prevented by dantrolene (3 μmol/L; n = 10). A single rapid infusion of DOX (10 mg/kg i.v.) reduced positive volumetric lymph flow to 29.7 ± 10.8% (n = 7) of baseline in mesenteric LVs in vivo. In contrast, flow in LVs superfused with dantrolene (10 μmol/L) only decreased to 76.3 ± 14.0% (n = 7) of baseline in response to DOX infusion. Subsequently, expression of the RYR1 subtype protein as the presumed dantrolene binding site was confirm in isolated mesenteric LMCs by flow cytometry.Conclusion and Implications: We conclude that dantrolene attenuates the acute impairment of lymph flow by DOX and suggest that its prophylactic use in patients subjected to DOX chemotherapy may lower lymphedema risk.

Safety of Rapid Infliximab Biosimilar Infusions in Patients With Inflammatory Bowel Disease

Background The biosimilar landscape for inflammatory bowel disease (IBD) continues to grow, with several biosimilar products for originator infliximab now available. The rapid infusion of originator infliximab and infliximab-dyyb has been shown to be well tolerated; however, the tolerability of rapid infusion in patients receiving infliximab-abda, another infliximab biosimilar, or in those who have switched among originator infliximab and biosimilars remains unknown. Objective We aimed to evaluate the safety of rapid infusion in patients with IBD who received infliximab-abda or underwent switches with infliximab products. Methods We conducted a retrospective observational study of all infliximab-related infusion encounters for patients ≥18 years with IBD who received their infusion over 30 to 90 minutes at our institution between March 1, 2020, and September 30, 2020. Patient, disease, and treatment characteristics were collected. The primary outcome was infusion reactions. Results A total of 377 infusion encounters for 96 unique patients were evaluated. Within the study cohort, 16% of patients were treated with originator infliximab, 42% with infliximab-dyyb, and 2% with infliximab-abda. The remaining 41% of patients received at least 2 infliximab products during the study period, primarily infliximab-dyyb and infliximab-abda. Approximately 54% and 42% of infusions encounters included premedication and immunomodulator use. Within the 377 infusion encounters, no infusion reactions were noted. Conclusion and Relevance Rapid infusion of infliximab biosimilars (including infliximab-abda) and in patients who have switched among originator infliximab and biosimilars is well tolerated. Future studies should assess clinical impact and outcomes of rapid infusion with biosimilars.

Reduced Intraoperative Blood Loss and Hypothermia in Burn Surgery using Cardiopulmonary Bypass Pumps

Objective: Patients presenting with total body surface area (TBSA) >40% burns require significant surgical treatment. Two substantial challenges during these surgeries are limiting blood loss and maintaining core temperatures. To overcome these challenges, several techniques have been developed, ranging from the Pitkin syringe method to the pneumatic tourniquet strategy for large-volume hyperthermic insufflation. Here, we compare the pneumatic tourniquet method to a roller pump method for maintenance of intraoperative normothermia and control of bleeding. Methods: We conducted a retrospective chart review of 20 patients presenting with TBSA >40% burns, 10 of whom were treated with the rapid infusion roller pump and 10 of whom were treated with the pneumatic tourniquet technique. Patients from each group were controlled for % TBSA, presence of inhalation injury, age, and date of admission. We reviewed transfusion requirement and the intraoperative temperatures, as well as the average intraoperative drop in temperature. Results: We observed improvement in the infusion volume, operative time, intraoperative temperature drop, minimum intraoperative temperature, estimated blood loss, and amount of required transfusion. Conclusions: Our study suggests that the rapid infusion roller pump technique is capable of achieving superior intraoperative bleeding control and temperature maintenance compared to the pneumatic tourniquet technique, resulting in decreased transfusion requirement.

A Budget Impact Analysis of Iron Polymaltose and Ferric Carboxymaltose Infusions

Objective: To compare the direct costs of ferric carboxymaltose (FCM) infusions, and iron polymaltose (IPM) infused via either a slow or rapid infusion; and explore potential savings associated with increased uptake of the least-expensive option at a local hospital.Setting: Hospital staff responsible for manufacturing, administering, and monitoring iron infusions, and the patients that received them at the Royal Hobart Hospital in 2018. Method: Frequency analysis identified the most prescribed iron infusion doses. A time-motion methodology was used to calculate the direct costs for each protocol at these doses. Finally, a budget-impact analysis of encouraging increased use of the least-expensive infusion protocol was conducted. Main outcome measures: Total direct costs for each infusion protocol at common doses. Potential budget savings associated with switching to the lowest costing of these infusion protocols where possible.Results: The most common doses were 0.5g, 1g, 1.5g and 2g. At these dose points, FCM infusions are the least expensive, but only if national health subsidies are applied. In cases where they do not apply, IPM prepared from ampoules and infused using the rapid protocol (‘IPM Ampoules Rapid’) is the least expensive. Switching all applicable FCM infusions and IPM infusions administered using the slow infusion protocol to IPM Ampoules Rapid is projected to yield up to $12,000 worth of savings annually.Conclusions: Increased use of the IPM Ampoules Rapid protocol when government-subsidised options are not available is projected to have cost-saving outcomes. Investigation of implementation strategies to increase the use of this protocol are warranted.